Administration of Oral Progesterone Capsules Rectally Instead of Orally for Greatly Improved Efficacy in Transfeminine People

By Aly W. | First published December 29, 2018 | Last modified June 27, 2022

Abstract / TL;DR

Oral progesterone achieves very low progesterone levels and produces only weak progestogenic effects due to bioavailability problems related to the oral first pass. Hence, non-oral progesterone, which bypasses the first pass and has much better bioavailability, is preferable. Most non-oral progesterone routes have problems such as unavailability and inconvenience however. Rectal progesterone is the most practical non-oral route, but progesterone suppositories are not available in most of the world. Oral progesterone capsules have been administered vaginally with success in cisgender women and theoretically could be useful via rectal administration similarly. Based on unpublished anecdotal clinical experience, this indeed may be the case—oral progesterone capsules administered rectally in transfeminine people have been reported to achieve much higher progesterone levels than oral administration and to allow for robust suppression of testosterone levels in combination with estradiol.


Oral progesterone has problems with first-pass metabolism and bioavailability such that it achieves very low progesterone levels and has only weak progestogenic effects (Aly W., 2018; Wiki). Non-oral progesterone, in contrast, can achieve much higher, physiological levels of progesterone, and hence is preferable to oral progesterone. Only a few non-oral routes of administration for progesterone are available and useful however. These routes of administration are specifically vaginal, rectal, and sublingual administration, as well as intramuscular and subcutaneous injection. Unfortunately, vaginal administration is not possible in most transfeminine people, sublingual administration has very limited availability throughout the world (marketed in Poland and Ukraine only), and injections have a short duration and need to be done once every 1 to 3 days—which is simply too frequent for most people. With these routes ruled out, the only route that is left is rectal progesterone.

Progesterone has been studied for use by rectal administration and is available in the form of suppositories (brand name Cyclogest) for use via this route in some countries. See here for general information on the pharmacokinetics of rectal progesterone. Unfortunately, no pharmaceutical rectal formulation of progesterone is available in the United States and many other countries. Pharmaceutical rectal progesterone appears to have only been marketed in “Cyprus, Hong Kong, India, Malaysia, Malta, Oman, Singapore, South Africa, Thailand, Tunisia, Turkey, the United Kingdom, and Vietnam” (Wiki). Hence, many transfeminine people throughout the world do not have a pharmaceutical rectal progesterone formulation available in their country. Some compounding pharmacies, for instance in the United States and Canada, produce and sell progesterone suppositories that can be used rectally. However, these are not approved pharmaceuticals, and availability may be limited in other countries.

Dr. Will Powers of Powers Family Medicine in Farmington Hills, Michigan in the United States has described the use of standard oral micronized progesterone, which is provided in the form of oil-filled capsules (brand names Prometrium, Utrogestan, and Microgest among others), via rectal administration in transfeminine people. His comments on this topic are spread about on Reddit (u/DrWillPowers), in the MTF Trans HRT Facebook group, and in Powers’s PowerPoint presentation on transgender healthcare. While many of Powers’s claims about transgender hormone therapy are problematic due to being inaccurate or based on low-quality information (see Aly W. (2019) for review), his statements in this area are based on objective blood test results from his clinical practice and have a certain level of value. Hence, I’ve opted to consolidate them in this article for informational purposes.

In any case, it should be cautioned that the excerpts in this article are unpublished and anecdotal. As such, the claims are unverified and should be considered with due skepticism. With that said however, rectal administration of progesterone using suppositories is a well-established route of administration of the medication and is known to achieve much higher progesterone levels than with oral administration of progesterone. Whereas oral progesterone produces progesterone levels that are subphysiological with accurate blood tests (Aly W., 2018; Wiki), rectal progesterone can readily achieve normal luteal-phase levels of progesterone (Wiki). In addition, oral micronized progesterone capsules have been administered vaginally in cisgender women with success in the published literature (Miles et al., 1994; Wang et al., 2019). The vaginal and rectal routes are said to have similar pharmacokinetics in general (Goletiani, Keith, & Gorsky, 2007; Wiki). For these reasons, there is good theoretical basis for rectal administration of oral progesterone capsules being an effective route of administration of progesterone.

Summary of Claims

The following is a summary of Powers’s comments on the use of oral micronized progesterone capsules (generic Prometrium) rectally instead of orally in his transgender clinical practice:

  • Powers usually uses 200 mg once per day at night before bed. He titrates to progesterone levels of 12 to 24 ng/mL with this route. He says that rectal administration of the capsules achieves “3x”, “4–16x”, “10–16x”, or “16x” higher levels than use via the oral route (he provides different figures in different comments). He says that sometimes progesterone levels are too high and require dose reduction to stay in the normal physiological range.
  • Powers says that the duration is short and that blood tests must be done within 12 to 24 hours of administration. However, he says that he has seen good levels in the peak female range at 18 to 24 hours after administration. He says that he hasn’t needed to administer it twice daily.
  • Powers says that some patients, for instance with chronic constipation or for some other reason, may have a dry rectum that doesn’t dissolve the capsules well. In these individuals, he says that the capsule may come out undissolved and broken in the morning upon a bathroom visit. He says that a solution to this problem is for the capsules to be punctured (e.g., with a pin) and/or wetted before administration, which can help with the dissolution.
  • In combination with estradiol, within 1 to 2 weeks of initiation, Powers says that rectal progesterone causes gonadotropin levels to drop to undetectable or near-undetectable levels and testosterone levels to be maximally suppressed in his transfeminine patients. He says that it’s useful for suppressing testosterone levels if they’re not fully controlled with other hormonal medications. Powers says that the specific regimens of estradiol that he’s typically added rectal progesterone to are 6 mg/5 days estradiol valerate by injection and 6 to 10 mg/day oral or sublingual estradiol. He says that when testosterone and gonadotropin levels aren’t already maximally suppressed with these estradiol regimens, adding rectal progesterone usually suppresses them the rest of the way.
  • Powers says that he’s had no reports of the sedation that occurs with oral progesterone with this route.
  • Powers also describes sublingual administration of oral micronized progesterone capsules and claims that this route achieves “4x” higher progesterone levels than oral administration.

Powers’s Original Comments

The following are Powers’s original comments from his PowerPoint, Reddit, and Facebook:

Micronized Oral Progesterone. […] I titrate to [progesterone levels of] around 12–24 ng/mL. Usual [progesterone] dose is 200 mg [sublingual] or rectal q.h.s. [(at bedtime)]. I’ve been using rectal dosing and found superior levels to [sublingual] or [oral]. Typically triples hormone level with the switch from oral to suppository. Half life is short so lab must be drawn within 12–24 hours of dosing. […] My current preferred regimen is to use the progesterone rectally at bedtime as a suppository (generic Prometrium). It seems to yield higher and more stable serum levels. Injectable progesterone does exist but would require daily injection to maintain levels due to the short half life. The slow absorption from the rectum seems to give the best steady state levels in regards to what I’ve encountered. (PowerPoint)

[I use] 100 mg Prometrium capsules or 200 mg. Depends on how well it’s tolerated. Using it rectally avoids first-pass oral metabolism. After a week or two on it FSH and LH drop to zero. Always. […] There is one rare exception. Dry-Trans-Butt syndrome. Occasionally someone with IBS-C or Sjogren’s or whatever will have a dry butt. They don’t have enough mucus/water to dissolve the capsule overnight and they poop it out intact in the morning. These people have to puncture it with a needle before placing it. Sometimes wet it as well. (Reddit)

Question: Does anyone know why [Powers] seems to only prescribe progesterone rectally? Answer (by Powers): Because the overwhelming majority of [progesterone administered orally] gets wiped out by the liver. When I started using it rectally, it avoids first-pass metabolism and the next day when I would draw the labs on the person in the evening (taking it q.h.s ([at bedtime])) people on oral versus people on rectal had a difference on serum [progesterone] level of about a factor of 10–16 in favor to rectal. It is overwhelmingly better. So much so that some people required a dose reduction to keep them within the band of what is physiologically normal. (Reddit)

Incidentally, I have found that the usage of rectal progesterone is actually superior to someone injecting it daily. I know that’s hard to believe, but I think it has to do with the fact that [progesterone] has such a short half-life and that it sort of dissolves out and coats the inside of the rectum resulting in a slow steady absorption. Once it’s injected, 4 hours later it’s [halved] out. (Reddit)

I prefer to use rectal progesterone as my [testosterone] blocker as it has [an antigonadotropic] effect and works as well as Lupron [(leuprorelin)]. If you have no FSH and LH your [testosterone] drops to zero anyway. (Reddit)

Estradiol valerate injections to suppress testosterone is my favorite starting method for new patients. I tend to use this now for 6 to 12 months on its own without [testosterone] blockers unless the patient specifically demands being put on a [testosterone] blocker. And that case I will put them on bicalutamide. Once they have some significant breast development I will add rectal progesterone to further finish off the testosterone if it has not dropped completely on its own. (Reddit)

It’s pretty well established in my PowerPoint that my preferred method is a year of injectable estrogen followed by rectal progesterone. I do not prescribe spironolactone anymore. For people who are really impatient I will use bicalutamide. (Reddit)

[Rectal progesterone] works for people who have wet butts, but some patients poop out a dry undissolved capsule in the morning, so again, variable. (Reddit)

Don’t use [progesterone] in a neovagina made from penile inversion. It’s just skin. Therefore stratified squamous epithelium and shitty at absorption. […] You might as well pop the cap and rub it on your wrist. […] Oh if it’s colon [(i.e., a colon neovagina)] it will work great. (Facebook)

Question: Given the half-life, do you see any benefit to splitting the dose between AM and PM dosage […]? Answer: Could be done. I’ve found good levels towards peak female range 18 to 24 hours after [the] last dose with rectal daily dosing [of progesterone]. Never had a need for b.i.d. [(twice daily)]. (Reddit)

Question: My oral [progesterone] is a gelcap, how does that work for sublingual administration? Doesn’t it all just… seep out? Answer: You crush it. But honestly using it rectally at bedtime is way better. Like 4x better levels in my experience. (Reddit)

Question: I’m currently taking Prometrium 100 mg daily (orally). If I’ve understood you correctly, you are suggesting [progesterone capsules be administered] rectally for better results? Answer: In my patients switching to rectal [progesterone] at bedtime from plain oral [progesterone] resulted in trough levels 4 to 16 times higher. [It resulted in] the elimination of some [testosterone] blocker drugs. (Reddit)

Question: Do you have any stats on the difference in blood levels between the three methods, or at least between [sublingual] and suppository? Answer: Oral 1x, [sublingual] 4x, and rectal 16x. (Reddit)

Question: Would/could using a non-water soluble lube when inserting the caps prevent proper absorption of the Prometrium caps? I got my levels tested a bit back when using the suppository method and they were ridiculously low, but I was using a small amount of vaseline as an aid at the time. Answer: Possibly.. the Prometrium is suspended in oil. The capsule is designed to break down in water. I have found some chronic constipation patients have some issues with levels and passing unbroken caps after many hours. I call this “trans dry butt syndrome” rather jokingly. I tell them to pierce it with a pin before insertion. Coating a cap designed to dissolve in water in a lipid could shield it from dissolving properly. (Reddit)

Question: I can’t think of a more sensitive way to ask this one, so: How important (if at all) is it that one evacuates their bowels before rectal admin of Prometrium caps? I couldn’t find any definitive answers here, but I imagine it could cause problems? Answer: I don’t think very. As long as it chills up there for 8 hours or so it seems to do the job whether poop is in town or not. [Once] dissolved it basically spreads and coats the area and is absorbed. The benefit of rectal is that it’s like a [sublingual] dose you hold for 8 hours perfectly. I think this slower absorption leads to improved and sustained levels unlike oral. (Reddit)

Question: When it comes to the rectal method, how far in should we be making sure to insert it? Is it just a matter of “if it’s not leaking out, it’s in far enough”, or is there an ideal minimum in terms of depth/something you should be feeling for? Answer: If its not leaking out, it’s in far enough. Once you hit “wet” a.k.a the mucosa, you’re good. (Reddit)

Question: Is it normal to not feel the same degree of quasi-“drunken” feeling when using it as a suppository? I figure that difference has to do with something unique to the way it’s metabolized via the oral route, but it seemed important to make sure it’s not still some sort of absorption issue (despite not using the vaseline anymore). Answer: I’ve never had this reported for either method, so this is new to me. Couldn’t tell you. (Reddit)

Question: How does progesterone affect [testosterone] exactly? Answer: As a mild [antigonadotropin] it interrupts the normal pulsatile [secretion of] GnRH which results in LH and FSH dropping a ton. With no signal of LH/FSH on the testicles they stop producing sperm and [testosterone]. (Reddit)

Question: What dosage are you using to try and get your patients to 12–25 ng/mL? Is that 200 mg micronized progesterone rectally, or a higher dose? Answer: 200 mg [progesterone] rectally q.h.s. [(at bedtime)]. (Facebook)

Question: When do you generally get blood tests for progesterone levels? Answer: I take them in the morning after using a rectal [progesterone]. (Facebook)

AW: You say that adding rectal P4 to E2 caused T, LH, and FSH to go to zero. What dose/route of E2 was that?

WP: Adding rectal P4 to E2 causes LH and FSH to drop. Usually to levels less than one. Testosterone never falls to zero because the adrenals still produce it. And I would say typically that level is around 6 mg every 5 days [EV by injection].

AW: I’m surprised that 6 mg/5 days EV by injection alone isn’t enough to maximally suppress T, LH, and FSH?

WP: It is, in many people. But in some people it’s not and the addition of [rectal] progesterone adds to that.

AW: So you don’t have much experience with rectal P4 added to oral or sublingual/buccal E2?

WP: I used to in the past. I don’t really do it anymore. In the past the dosage of oral/sublingual E2 was usually around 6 to 10 mg a day. That was when I used [rectal] progesterone as a blocker, but I haven’t done that in a few years. I just haven’t found it necessary.

AW: So rectal P4 added to 6–10 mg/day oral/sublingual E2 likewise caused T, LH, and FSH to go to “zero” in those in whom they weren’t already maximally suppressed?

WP: To less than one. But yes. That was what I observed for a long time.

(Personal communication, Feb. 16th, 2021)